Process for the preparation of fluoro compounds from the corresponding amines

ABSTRACT

Compounds containing a primary amino group are converted into compounds containing a fluorine atom in place of the amino group by reaction of the amino compound with hydrogen fluoride and a nitrosating reagent under the influence of ultrasound or microwaves.

This is a national stage application of PCT/GB97/01201, filed May 1,1997.

This invention relates to the preparation of fluoro compounds fromamines by replacement of the amino group by a fluorine atom.

It is known to produce fluoro compounds from corresponding amines,particularly aromatic amines, by conversion of the latter into adiazonium tetrafluoroborate salt which is then decomposed thermally toproduce the fluoro compound. It is also known to carry out thediazotization of aromatic amines in anhydrous hydrofluoric acid withsubsequent heating to produce the corresponding fluoro compound. Neitherof these methods is entirely satisfactory. The first involves isolationof the tetrafluoroborate salt which is hazardous and time consuming. Thelatter method gives poor yields when substituted aromatic amines areused, especially if the substitution is in the ortho position. Also, thereaction has to be carried out under pressure because anhydroushydrofluoric acid is volatile.

There have been a number of proposals of methods for the production offluoro compounds which are said to give improved results. For example,European Specification EP-A-0430434 (Imperial Chemical Industries plc.)describes a process for the preparation of fluoro aromatic and fluoroheteroaromatic compounds by reaction of corresponding aromatic orheteroaromatic amines with a nitrosyl polyfluoro salt in an inert liquidfollowed by decomposition of the diazonium polyfluoro salt obtained insitu. It has also been proposed (M{umlaut over (u)}eller et al Z. Chem.26 (1986) pp 169-170) to bring about the decomposition of aromaticdiazonium fluoroborates in a fluorinated hydrocarbon reaction medium inthe presence of Et₃N.3HF under the influence of ultrasound at 40° C. Itis stated that high yields may be obtained. However, this method likeother known methods involving the use of diazonium tetrafluoroborates,requires isolation of the tetrafluoroborate salt.

It has now been found that compounds containing a primary amino groupcan be converted into compounds containing a fluorine atom in place ofthe amino group without isolation of any intermediate diazonium salt andwith excellent yields of the desired product, if the reaction is carriedout with ultrasound.

The present invention accordingly provides a process for converting acompound containing a primary amino group into a compound containing afluorine atom in place of the said amino group which comprisescontacting the said amino group containing compound with hydrogenfluoride, or with a complex thereof with a base, and with a nitrosatingagent, at a temperature in the range of −20° to +100° C. while thereagents are subjected to the action of ultrasound having a frequency of10-100 kHz and an intensity of at least 20 watts/cm² and/or microwaveshaving a frequency of 300 MHz to 3 GHz and an intensity of 100 W to 5kW.

This process is applicable to a wide variety of amino group containingcompounds including more particularly aromatic and heteroaromaticprimary amines and alpha-amino acids.

The invention may be, for example, applied to aromatic amino-compoundsof the formula

A(NH₂)_(n)

where A is an unsubstituted or substituted aromatic or heteroaromaticradical and n is an integer, e.g. from 1 to 4. A may be for example aresidue of benzene, naphthalene, diphenyl, acetonaphthene, fluorene, orpyrene or a heteroaromatic compound such as pyridine or quinoline.

The invention may also be applied to α-amino acids such as alanine,valine, phenylalanine, isoleucine, tyrosine, and threonine, and toaralkylamines such as phenylethylamine.

Examples of suitable aromatic and heteroaromatic amines which may besubjected to the process of the present invention may be represented bythe general formula:

where Ar is phenyl, α- or β-naphthyl, pyridyl, quinolyl, thienyl, ordiphenyl, n is 0, 1, 2 or 3 and R is halogen, alkyl, hydroxy, alkoxy,COOH, CHO, alkoxycarbonyl, nitro, cyano, trifluoromethyl, carbamoyl,alkylcarbamoyl, dialkylcarbamoyl, sulphonamido, alkanoyl, or aroyl.

Preferred aromatic primary amines which may be used in the process ofthe invention conform to the general formula:

where n is 0, 1, 2 or 3 and the radicals R, which may be the same ordifferent when n is 2 or 3, are each halogen, e.g. fluorine or chlorine,alkyl of 1 to 4 carbon atoms, e.g. methyl or ethyl, hydroxy, alkoxy of 1to 4 carbon atoms, e.g. methoxy or ethoxy, alkylthio of 1 to 4 carbonatoms, e.g. methylthio, carboxy, alkoxycarbonyl with 1 to 4 carbon atomsin the alkoxy, nitro, cyano or trifluoromethyl.

The hydrogen fluoride is preferably introduced into the reaction mixturein the form of a complex with a base which is preferably a secondary ortertiary aliphatic amine, a heterocyclic aromatic amine, or an ether.Examples of suitable compounds are triethylamine, diisopropylamine,pyridine, tetrahydrofuran, diethyleneglycol dimethyl ether,1,3-dioxolane, and dioxane.

The nitrosating reagent is preferably an alkali metal nitrite, e.g.sodium nitrite, or a nitrite ester, e.g. ethyl nitrite. It is alsopossible to use other nitrosating agents, for example nitrosylfluoroborate or nitrogen oxides.

In some cases improved yields are obtained by incorporating borontrifluoride etherate into the reaction mixture.

The amount of nitrosating reagent which is used in the process can bevaried within wide limits. Preferably from 1.0 to 5.0, especially from1.0 to 2.0 and more especially from 1.1 to 1.5, mole of nitrosatingreagent is used per mole of primary amine.

The amount of hydrogen fluoride complex to primary amine can be carriedwithin wide limits. Preferably 5 to 200, especially 10 to 50 and moreespecially 10 to 25, parts of liquid are used per part of primary amine.

The reaction may be carried out at any temperature in the range −20° C.to +150° C., but it is preferably carried out at 0 to 70° C., andespecially at 0 to 50° C. The pressure is not critical and it isordinarily convenient to carry out the reaction at ambient pressure.

The ultrasound or microwaves may be provided using commerciallyavailable sources, e.g. an ultrasonic cleaning bath or a microwave oven.The frequency of the ultrasound should be chosen to maximise absorptionof energy by the reaction medium. Typically, the ultrasound should havean intensity of at least 20, preferably 50, more preferably 100 andespecially 200 W/cm². Microwaves should have a frequency of 300 MHz to3GHz and a power of 200 W to 5 kw. (In some countries, the maximumfrequency is fixed by law.)

Following completion of the reaction (shown by disappearance of thestarting amine and the intermediate diazonium salt from the reactionmedium) the desired fluoro compound may be worked up in the usual way.

The fluoro compounds obtained are useful as intermediates in themanufacture of a wide range of products including pharmaceuticals,herbicides, pesticides, dyestuffs and plastics.

The following Examples illustrate the invention.

EXAMPLE 1 Diazotization of 2,4,6-trimethylaniline in Et₃N-3HF

2,4,6-Trimethylaniline (2.3 g, 0.02 mol) was syringed over a period of30 minutes into Et₃N-3HF (30 cm³) at 0° C. in a 100 cm³ 3-necked glassflask, which had been placed in an operating ultrasonic bath (typeT460/H (285 watts). The addition of sodium nitrite (2.0 g, 0.03 mol) in200 mg portions at 0° C. caused the reaction mixture to turn initiallyto a yellow colour which progressively darkened. Very little tar wasformed during the reaction. The mixture was then allowed to warm to roomtemperature and was exposed to ultrasound for 20 minutes more. Thereaction mixture had now turned brown and very little undissolved sodiumnitrite could be seen in the solution. The mixture was poured into water(150 cm³) and the product extracted with diethyl ether (200 cm³) anddried over magnesium sulphate.

Following fractional distillation to remove the diethyl ether a red oilwas isolated, which was distilled at 150-153° C. @ atmospheric pressure.The distillation was complete in 45 minutes affording1-fluoro-2,4,6-trimethylbenzene (2.1 g, 89.3%) as a colourless liquid.

The ¹H n.m.r. spectrum contained signals at δ_(H) (CDCl₃) 2.31, 2-CH₃and 6-CH₃ (d, J=2.0 Hz, 6H); 2.32, 4-CH₃ (s, 3H); 6.88, 3-H and 5-H (d,J=7.0 Hz, 2H). The ¹⁹F n.m.r. spectrum had a signal at δ_(F) (CDCl₃)127.8, 1-F (s).

The mass spectrum produced a molecular ion at m/z 138 and the expectedfragmentation pattern for 1-fluoro-2,4,6-trimethylbenzene at m/z 123,109, 97, 91 and 83.

EXAMPLE 2 Diazotization of 2,6-dimethylaniline in Et₃N-3HF

The diazotization of 2,6-dimethylaniline (2.3 g, 0.02 mol) was performedunder the same conditions as described for 2,4,6-trimethylaniline inExample 1. The reaction mixture turned yellow during the initialaddition of sodium nitrite (2.0 g, 0.03 mol) and gradually turned redwith the increased addition of sodium nitrite. Some tar was formed whichwas easily extracted with solvent. The work-up was identical to thatdescribed for 2,4,6-trimethylaniline. Diethyl ether (150 cm³) was usedfor the extraction of the organic layer from the aqueous washings. Theorganic extract was dried over magnesium sulphate.

Fractional distillation of the solvent formed an orange oil which wasdistilled at 141-143° C. @ atmospheric pressure affording1-fluoro-2,6-dimethylbenzene (2.0 g, 86.3%) as a colourless liquid. Thedistillation was complete in 1 hour.

The ¹H n.m.r. spectrum contained signals at δ_(H) (CDCl₃) 2.25, 2-CH₃and 6-CH₃ (d, J=2.0 Hz, 6H); 6.91, 3-H and 5-H (dd, J=8.3 Hz and J=6.5Hz. 2H) and 7.01, 4-H (t, J=8.0 Hz, 1H). The ¹⁹F n.m.r. spectrum had asignal at δ_(F) (CDCl₃) 122.5, 1-F (ts, J=6.5 Hz and J=2.0 Hz).

The mass spectrum produced a molecular ion at m/z 124 and the expectedfragmentation pattern for 1-fluoro-2,6-dimethylbenzene at m/z 109, 103,96, 89, 83 and 77.

EXAMPLE 3 Diazotization of 2,5-dimethylaniline in Et₃N-3HF

2,5-Dimethylaniline (2.3 g, 0.02 mol) was syringed into Et₃N-3HF (30cm³) over a 35 minute period. The reaction mixture turned red during theaddition of sodium nitrite (2.0 g, 0.03 mol) and a significant amount ofnitrogen was evolved during the reaction. Although a high proportion ofsodium nitrite was seen to dissolve a greater proportion of tarrymaterial was formed. The mixture was poured into water (150 cm³) and theremaining contents of the flask washed with further water (30 cm³×2).The mixture was extracted with diethyl ether (150 cm³×2) and the organiclayer dried over magnesium sulphate.

Fractional removal of diethyl ether afforded an orange oil. Distillationof the oil at 144-146° C. @ atmospheric pressure afforded1-fluoro-2,5-dimethylbenzene (1.52 g, 65.5%) as a clear colourlessliquid.

The ¹⁹F n.m.r. spectrum had a signal at δ_(F) (CDCl₃) 121.9, 1-F (ddq,J=8.5 Hz, J=10.5 Hz and J=2.2 Hz). From the GC/MS the compound showedthe expected molecular ion at m/z 124 and the expected fragmentation for1-fluoro-2,5-dimethylbenzene at m/z 109, 101, 96, 83 and 77.

EXAMPLE 4 Diazotization of 2,4-dimethylaniline in Et₃N-3HF

A similar approach was used for the diazotization of 2,4-dimethylanilineas that described in Example 1. Addition of sodium nitrite (2.0 g, 0.03mol) to 2,4-dimethylaniline (2.3 g, 0.02 mol), initially formed a yellowcolour which eventually turned orange. Diazotization became evidentafter 20 minutes when the evolution of gas was vigorous. Very littleundissolved sodium nitrite was detected at the end of the reaction.

Work-up as described in Example 1 for 2,4,6-trimethylaniline formed abrown oil on distillation of diethyl ether. Distillation of the oil at143-144° C. @ atmospheric pressure afforded 1-fluoro-2,4-dimethylbenzene(1.73 g, 74.6%) as a clear liquid.

The ¹H n.m.r. spectrum contained signals at δ_(H) (CDCl₃) 2.23, 2-CH₃(d, J=1.8 Hz, 3H); 2.28, 4-CH₃ (s, 3H); 6.87, 6-H (t, J=9.0 Hz, 1H);6.92, 5-H (ddd, J=8.0 Hz, J=5.5 Hz and J=2.0 Hz, 1H) and 6.97, 3-H (dm,J=7.8 Hz and J=2.0 Hz, 1H). The ¹⁹F n.m.r. spectrum has a signal atδ_(F) (CDCl₃) 124.2, 1-F (complex m).

The mass spectrum produced a molecular ion at m/z 124 and the expectedfragmentation pattern for 1-fluoro-2,4-dimethylbenzene at m/z 109, 101,96, 89, 83 and 77.

EXAMPLE 5 Diazotization of 2,3-dimethylaniline in Et₃N-3HF

2,3-Dimethylaniline (2.3 g, 0.02 mol) was syringed into Et₃N-3HF (30cm³) at 0° C. The addition of sodium nitrite (2.0 g, 0.03 mol) causedthe evolution of gas under the influence of ultrasound, which wassignificant during the first 25 minutes. The clear reaction mixturegradually turned yellow and progressively darkened with the formation oftar. The brown mixture was poured into water (150 cm³) and extractedwith diethyl ether (180 cm³×2). The remaining tarry residue wastransferred to a Soxhlet apparatus and extracted repeatedly with diethylether (30 cm³) over 24 hours. The ether extracts were dried overmagnesium sulphate and fractional removal of diethyl ether afforded abrown oil.

Distillation of the oil at 142-143° C. @ atmospheric pressure afforded1-fluoro-2,3-dimethylbenzene (1.47 g, 63.4%) as a clear liquid.

The ¹H n.m.r. spectrum had signals at δ_(H) (CDCl₃) 2.18, 2-CH₃ (d,J=2.0 Hz, 3H); 2.28, 3-CH₃ (s, 3H); 6.88, 6-H (t, J=7.6 Hz, 1H) and6.91, 4-H (d, J=7.6 Hz, 1H) and 7.03, 5-H (q, J=8.0 Hz and J=6.0 Hz,1H). The ¹⁹F n.m.r. spectrum had a signal at δ_(F) (CDCl₃) 118.3, 1-F(tq, J=7.6 Hz and J=2.0 Hz).

The mass spectrum produced a molecular ion at m/z 124 and the expectedfragmentation pattern for 1-fluoro-2,3-dimethylbenzene at m/z 109, 101,96, 86, 83 and 77.

EXAMPLE 6 Diazotization of 3,4-dimethylaniline in Et₃N-3HF

3,4-Dimethylaniline (2.3 g, 0.02 mol) was added to Et₃N-3HF inproportions (0.15 g) over a 40 minute period at 0° C. Sodium nitrite(2.3 g, 0.03 mol) was added in small quantities (100 mg) under theinfluence of ultrasound. The slow addition of both substrates helped toreduce the formation of tar. After the complete addition of bothsubstrates, the reaction vessel was allowed to warm to room temperatureand ultrasound was applied for a further 10 minutes. The mixture waspoured into water (100 cm³). The organic layer was extracted withdiethyl ether (150 cm³×2) and dried over magnesium sulphate.

Fractional distillation of the solvent afforded a brown oil which wasdistilled at 138-139° C. @ atmospheric pressure affording1-fluoro-3,4-dimethylbenzene (1.30 g, 56.1%) as a clear liquid. Attemptswere made to extract any material with a Soxhlet apparatus, but suchmeasures did not improve the isolated yield of the product. The ¹⁹Fn.m.r. spectrum had a signal at δ_(F) (CDCl₃) 120.1, 1-F (dddq, J=6.0Hz, J=9.6 Hz, J=8.6 Hz and J=1.0 Hz). From the GC/MS the compound showedthe expected molecular ion at m/z 124 and the expected fragmentation for1-fluoro-3,4-dimethylbenzene at m/z 109, 101, 97, 83 and 77.

EXAMPLE 7 Diazotization of 4-fluoroaniline in Et₃N-3HF

4-Fluoroaniline (2.3 g, 0.02 mol) was syringed over a period of 25minutes into Et₃N-3HF at 0° C. under the influence of ultrasound. Theaddition of sodium nitrite (2.0 g, 0.03 mol) in 150 mg portions causedthe reaction mixture to adopt an orange colour which progressivelydarkened with the formation of a small quantity of tar. During theinitial addition of sodium nitrite there was evolution of gas. Themixture was then allowed to warm to ambient temperature and exposed toultrasound for a further 25 minutes. The reaction contents were pouredinto water and the organic constituents were extracted with diethylether (200 cm³). The ether extract was dried over magnesium sulphate andfractional distillation of solvent afforded a brown oil.

Distillation of the oil at 88-90° C. @ atmospheric pressure afforded1,4-difluorobenzene (1.49 g, 63.1%) as a clear liquid. The i.r. spectrumcontained major peaks at υ_(max) 3079 cm⁻¹ (υ_(ArC—H)); 1625-1573 cm⁻¹(υ_(ArC═C)) and 1409-957 cm⁻¹ (υ_(C—F)). The ¹H n.m.r. spectrumcontained signals at δ_(H) (CDCl₃) 7.05-7.21, 2-H, 3-H, 5-H and 6-H (dd,J=6.0 Hz and J=6.0 Hz, 4H). The ¹⁹F n.m.r. spectrum had a signal atδ_(F) (CDCl₃) 120.8, 1-F, 4-F (tt, J=6.0 Hz and J=6.0 Hz).

The mass spectrum produced a molecular ion at m/z 114 and the expectedfragmentation pattern for 1,4-difluorobenzene at m/z 94, 88, 81, 75 and70.

EXAMPLE 8 Diazotization of 2-fluoroaniline in Et₃N-3HF

The diazotization of 2-fluoroaniline (2.3 g, 0.02 mol) was performedunder the same conditions as those described for 4-fluoroaniline.Addition of sodium nitrite (2.0 g, 0.03 mol) caused the evolution ofgas. The clear reaction mixture initially turned yellow and graduallydarkened to a red colour. Some tar was formed during addition of sodiumnitrite which was partially extracted with diethyl ether (30 cm³). Thereaction mixture was poured into water (150 cm³) and extracted withdiethyl ether (300 cm³). The combined ether extracts were dried overmagnesium sulphate and fractional distillation of the solvent afforded ared oil.

Distillation of the oil at 88-90° C. @ atmospheric pressure afforded1,2-difluorobenzene (1.32 g, 55.9%) as a clear colourless liquid.

The i.r. spectrum contained major peaks at υ_(max) 3080 cm⁻¹(υ_(ArC—H)); 1620-1570 cm⁻¹ (υ_(ArC═H)) and 1401-900 cm⁻¹ (υ_(C—F)) andthe ¹H n.m.r. spectrum showed signals at δ_(H) (CDCl₃) 7.05-7.25(complex m). The ¹⁹F n.m.r. spectrum had a signal at δ_(F) (CDCL₃)138.9, 1-F, 2-F (ddd, J=9.0 Hz, J=9.0 Hz and J=5.5 Hz).

The mass spectrum produced a molecular ion at m/z 114 and the expectedfragmentation pattern for 1,2-difluorobenzene at m/z 94, 88, 81, 75, 70and 63.

EXAMPLE 9 Diazotization of Aniline in Et₃N-3HF

A similar approach was used for diazotization of aniline as described inpreparation Example 7 except aniline (2.3 g, 0.03 mol) was added over a30 minute period to Et₃N-3HF at 0° C. Addition of sodium nitrite (2.3 g,0.03 mol) caused the evolution of gas. The reaction mixture turned redin colour, which gradually darkened with the formation of some tar. Thecontents were allowed to warm to room temperature and ultrasound wasapplied for a further 20 minutes. The reaction mixture was poured intowater (150 cm³) and extracted with diethyl ether (250 cm³). The tarrymaterial was extracted with diethyl ether (20 cm³) and finally washedwith water (10 cm³). The combined extracts were dried over magnesiumsulphate and fractional evaporation of solvent afforded a brown oil.

Distillation of the oil at 80-81° C. @ atmospheric pressure affordedfluorobenzene (1.30 g, 54.8%) as a clear liquid.

The i.r. spectrum contained major peaks at υ_(max) 3075 cm⁻¹(υ_(ArC—H)); 1610-1574 cm⁻¹ (υ_(ArC═H)) and 1415-911 cm⁻¹ (υ_(C—F)). The¹H n.m.r. spectrum showed signals at δ_(H) (CDCl₃) 7.05, 2-H and 6-H (t,J=8.5 Hz, further splitting J=1.0 Hz, 2H); 7.13, 4-H (t, J=6.3 Hz, 1H);7.33, 3-H and 5-H (tdq, J=7.5 Hz, J=7.0 Hz and J=2.0 Hz, 2H). The ¹⁹Fn.m.r. spectrum had a signal at δ_(F) (CDCl₃) 113.5, 1-F (ttd, J=9.1 Hz,J=5.5 Hz and J=1.5 Hz).

The mass spectrum produced a molecular ion at m/z 96 and the expectedfragmentation pattern for fluorobenzene at m/z 92, 75, 70 and 63.

EXAMPLE 10 Preparation of 1,2-difluorobenzene in HF/THF with Ultrasound

An FEP container was initially cooled to −78° C. with acetone/Drikoldand carefully charged with HF/THF (4:1). 2-Fluoroaniline (5.0 g, 0.05mol) was added to the HF/THF mixture under vigorous stirring and allowedto warm to −10° C. When the desired temperature was reached thecontainer was transferred to an ultrasonic bath containing an ice-saltwater mixture. The container was fitted with a Drikold condenser adaptedwith a polypropylene filter funnel.

Sodium nitrite (4.95 g, 0.07 mol) was added over 35 minutes under theinfluence of ultrasound. During the addition an exothermic reactionoccurred with the evolution of a brown gas. The ultrasound was appliedfor a further 1 hour after the complete addition of sodium nitrite atroom temperature. The mixture was further heated for 1 hour at 45° C.under the influence of ultrasound. Dediazoniation was complete after 1hour. The mixture was poured onto iced water (150 cm³). The organicconstituents were extracted with dichloromethane (200 cm³×2). Theextracts were finally washed with water (100 cm³), stirred with sodiumfluoride (2.5 g) and dried with magnesium sulphate for 12 hours.

The solvent was removed by fractional distillation which afforded a redoil. Distillation of the oil @ atmospheric pressure afforded a clearliquid of 1,2-difluorobenzene at 88-91° C. (2.92 g, 56.9%).

The i.r. ¹H n.m.r., ¹⁹F n.m.r and mass spectrometery results weresimilar to those from Example 8 which confirmed the formation of1,2-difluorobenzene. Without ultrasound the yield is only 24%.

EXAMPLE 11 Preparation of 1,4-difluorobenzene in HF/THF with Ultrasound

An FEP container was cooled to −78 ° C. and HF followed by THF was addedin a ratio of 4:1. 4-Fluoroaniline (5.0 g, 0.05 mol) was added to theHF/THF under vigorous stirring. After the complete addition the reactionmixture was allowed to warm to −10° C. and fitted with a Drikoldcondenser. The reaction mixture was placed in an ultrasonic bathcontaining ice-salt water mixture. Sodium nitrite (4.95 g, 0.07 mol) wasadded in portions (90 mg) over 1 hour under the influence of ultrasound.The addition caused evolution of a brown gas which became significantafter 30 minutes. Ultrasound was applied for a further 1 hour at roomtemperature and then heated at 45° C. for another 1 hour.

The following work-up was similar to that described in Example 10.Fractional removal of dichloromethane afforded an orange oil.Distillation of the oil @ atmospheric pressure afforded to clear liquidof 1,4-difluorobenzene at 87-88° C. (3.16 g, 62.0%). Without ultrasound,the yield is only 40%.

EXAMPLES 12 AND 13

The addition of BF₃-etherate complex has helped to improve the yield ofisolated 1,2-difluorobenzene and 1,4-difluorobenzene as shown below.

Substrate Product Yield % Conditions 2-fluoroaniline 1,2-difluorobenzene60 NaNO₂, BF₃ etherate with ultrasound 4-fluoroaniline1,4-difluorobenzene 68 NaNO₂, BF₃ etherate with ultrasound

The procedures used for these reactions are similar to Examples 10 and11. 5 cm³ of the BF₃ etherate complex were used.

EXAMPLES 14, 15 and 16

Proceeding as in Example 1, the following α-amino acids were convertedinto the corresponding α-fluoroacids in the stated yields:

Example 14 β-alanine 50% Example 15 DL-Valine 75% Example 16L-phenylalanine 70%

EXAMPLES 17 TO 22

The reactions were carried out as described in Example 1 except that, inplace of the ultrasonic bath, a microwave oven operating at 2.45 GHzwith a 720W output, was used. The following amino-compounds wereconverted into the corresponding fluorocompounds in the stated yields:

Example 17 β-alanine 65% Example 18 DL-valine 60% Example 19L-phenylalanine 69% Example 20 L-Isoleucine 57% Example 21 L-Tyrosine40% Example 22 (+)α-Phenylethylamine 63%

What is claimed is:
 1. Process for converting a compound containing aprimary amino group into a compound containing a fluorine atom in placeof said amino group which comprises contacting saidamino-group-containing compound with hydrogen fluoride, or with acomplex thereof with a base, and a nitrosating reagent at a temperaturein the range −20° to +150° C. while subjecting the reagents to theaction of ultrasound having a frequency of 10 to 100 kHz and anintensity of at least 20 Watts/cm² or to the action of microwaves havinga frequency of 300 MHz to 3GHz and an intensity between 100 W and 5 kW.2. Process according to claim 1 wherein the amino-group-containingcompound in an aromatic or heteroaromatic primary amine or anα-amino-acid.
 3. Process according to claim 1 wherein theamino-group-containing compound is a compound of formula

where n is 0, 1, 2 or 3 and the radicals R, which may be the same ordifferent when n is 2 or 3, are each halogen, alkyl of 1 to 4 carbonatoms, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms,carboxy, alkoxycarbonyl with 1 to 4 carbon atoms in the alkoxy, nitro,cyano or trifluoromethyl.
 4. Process according to claim 1 wherein ahydrogen fluoride complex is used in which the base is a secondary ortertiary aliphatic amine, a heterocyclic aromatic amine, or an ether. 5.Process according to claim 4 wherein the said base is trimethylamine,diisopropylamine, pyridine, tetrahydrofuran diethyleneglycol dimethylether, 1,3-dioxolane or dioxane.
 6. Process according to claim 1 whereinthe nitrosating reagent is an alkali metal nitrite or a nitrite ester.7. Process according to claim 1 wherein the reaction is carried out inthe presence of boron trifluoride etherate.
 8. Process according toclaim 1 wherein the reaction temperature is 0° to 50° C.